Lipids are major components of all cellular membranes. Eukaryotic organisms contain an especially large variety of these substances, such as phosphoglycerides, sphingolipids and glycolipids. Relatively little is known about the biogenesis and function of the membrane lipids of animal cells. A better understanding of this aspect of membrane biochemistry would be desirable, since lipid abnormalities are found in many disease states, which include the hyperlipoproteinemias, diabetes, and the sphingolipidoses. As an approach to this problem, we wish to isolate mutants of animal cells grown in tissue culture, which are defective in specific enzymes of membrane lipid biogenesis. In particular, the present work will focus on the role of the so-called "polar headgroups" of the phosphoglycerides, mutants in the synthesis of which have not been previously isolated in animal cells. From a comparison of the growth, composition and membrane function of the mutants with normal cells, it is likely that an understanding of lipid regulation and function will emerge. The present work will not overlap with the nutritional modifications of lipid composition, recently described by Vagelos and coworkers. Indeed, the approach described here will complement these earlier nutritional studies. The technique for isolating such animal cell mutants is a direct extension of an autoradiographic screening assay, previously developed by the PI for bacteria (Raetz, P.N.A.S. 72, 2274, 1975), which has recently been found to be equally useful for colonies of Chinese hamster ovary cells grown in tissue culture (Esko and Raetz, Science, in preparation).